Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

An overview of heat stress in Chickpea (<em>Cicer arietinum</em> L.): effects, mechanisms and diverse molecular breeding approaches for enhancing resilience and productivity

Fri, 24/01/2025 - 12:00
Mol Breed. 2025 Jan 21;45(2):18. doi: 10.1007/s11032-025-01538-4. eCollection 2025 Feb.ABSTRACTChickpea (Cicer arietinum. L) holds the esteemed position of being the second most cultivated and consumed legume crop globally. Nevertheless, both biotic and abiotic constraints limit chickpea production. This legume is sensitive to heat stress at its reproductive stage leading to reduced flowering, flower abortion, and lack of pod formation, therefore emerging as a major limiting factor for yield. Chickpea, predominantly cultivated in semi-arid regions, is frequently subjected to high-temperature stress, which adversely affects its growth and yield. Given the escalating impacts of climate change, the development of heat-tolerant chickpea genotypes is imperative and can be achieved through the integration of advanced biotechnological approaches. The appropriate solution devised by some researchers is the modification of genetic architecture by targeting specific genes associated with tolerance to heat stress and harnessing them in the development of more robust chickpea varieties. Besides this, multi-omics strategies (Genomics, Transcriptomics, Proteomics, and Metabolomics) have made it easier to reveal the distinct genes / quantitative trait loci (QTLs) / markers, proteins, and metabolites correlated with heat tolerance. This review compiles noteworthy revelations and different tactics to boost chickpea tolerance under heat temperatures.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-025-01538-4.PMID:39850651 | PMC:PMC11751345 | DOI:10.1007/s11032-025-01538-4

Gut microbiota and plasma metabolites in pregnant mothers and infant atopic dermatitis: A multi-omics study

Fri, 24/01/2025 - 12:00
World Allergy Organ J. 2025 Jan 2;18(1):101017. doi: 10.1016/j.waojou.2024.101017. eCollection 2025 Jan.ABSTRACTBACKGROUND: Many studies reported the influence of infants' gut microbiota on atopic dermatitis (AD) postnatally, yet the role of maternal gut microbiota and plasma metabolites in infants' AD remains largely unexplored.METHODS: Sixty-three pregnant mother-infants were enrolled and followed after childbirth in Guangzhou, China. Demographic information, maternal stool and plasma samples, and records for infants' AD were collected. Maternal gut microbiota/metabolome and plasma metabolome were profiled using shotgun metagenomics and non-targeted metabolomics. Logistic regression and multi-omics analysis were used to explore characteristic maternal gut microbiota in the AD and health groups.RESULTS: The α-diversity of maternal gut microbiota in health group was significantly higher than AD group (Shannon diversity P = 0.02, Simpson diversity P = 0.04). Short-chain fatty acids (SCFAs) producing microorganisms, including Faecalibacterium, Roseburia, Butyricicoccus, and Ruminococcus, as well as the abundance of phenylalanine, tyrosine, and tryptophan biosynthesis pathway, were enriched in health group (LDA>2 and P < 0.05). Virulent factors (VFs) involved in immune modulation were enriched in the health group, while VFs involving in adhesin were enriched in the AD group (P < 0.05). Metabolomic analysis showed that a polyunsaturated fatty acid/linoleic acid, 13S-hydroxyoctadecadienoic, were negatively associated with AD in both the gut and plasma samples (FDR<0.05). Several other linoleic acids and flavonoids were negatively associated with AD (FDR<0.05). Neural network analysis revealed that microorganisms enriched in health group may produce these protective fatty acids.CONCLUSIONS: Our findings show that maternal gut microorganisms/metabolites and plasma metabolites during pregnancy impact subsequent pathogenesis of infants AD. This illuminates new strategies against early AD in offspring.PMID:39850616 | PMC:PMC11754505 | DOI:10.1016/j.waojou.2024.101017

Integrated skin metabolomics and network pharmacology to explore the mechanisms of Goupi Plaster for treating knee osteoarthritis

Fri, 24/01/2025 - 12:00
J Tradit Complement Med. 2024 Apr 12;14(6):675-686. doi: 10.1016/j.jtcme.2024.04.004. eCollection 2024 Nov.ABSTRACTBACKGROUND AND AIM: Goupi Plaster (GP) is topical traditional Chinese medicine preparation. It has been used to treat Knee Osteoarthritis (KOA) in clinical practice of traditional Chinese medicine (TCM). However, the mechanisms of GP relieve KOA are poorly understood.EXPERIMENTAL PROCEDURE: Rabbit models of KOA were established and treated with GP. Knee cartilage pathology was analyzed using hematoxylin and eosin staining, while plasma levels of inflammatory factors (interleukin (IL)-4, IL-6, and IL-17) and skin neurotransmitters (calcitonin gene-related peptide (CGRP), substance P (SP), and5-hydroxytryptamine (5-HT)) were measured by enzyme linked immunosorbent assay. Metabolomics based on GC-TOF-MS analysis screened for skin biomarkers as well as relevant pathways. Network pharmacology screened for relevant skin targets as well as relevant pathways, and finally, MetScape software was utilized to integrate the results of metabolomics and network pharmacology to screen for key skin targets, key metabolites, and key pathways for GP treatment of KOA.RESULTS AND CONCLUSION: GP administration substantially repaired cartilage surface breaks in KOA and led to relatively intact cartilage structure and normal cell morphology. GP decreased plasma levels of IL-6 and IL-17 and skin levels of CGRP, SP and 5-HT while increased plasma IL-4. GP administration normalized the levels of 15 metabolites which were changed in KOA. Network pharmacology analysis identified 181 targets. Finally, 3 key targets, 5 key metabolites and 3 related pathways were identified, which suggested that GP improved skin barrier function and skin permeability by regulating skin lipid metabolism. GP treatment also regulated skin amino acid levels and subsequently affected neurotransmitters and signaling molecules. In addition, the purinergic signaling pathway was also involved in the treatment of GP against KOA.In conclusion, GP treatment is associated with changes in skin lipid metabolism, neurotransmitters, and the purinergic signaling pathway.PMID:39850603 | PMC:PMC11752118 | DOI:10.1016/j.jtcme.2024.04.004

Multi-omics approaches to deciphering complex pathological mechanisms of migraine: a systematic review

Fri, 24/01/2025 - 12:00
Front Pharmacol. 2025 Jan 9;15:1452614. doi: 10.3389/fphar.2024.1452614. eCollection 2024.ABSTRACTBACKGROUND: Migraine represents a chronic neurological disorder characterized by high prevalence, substantial disability rates, and significant economic burden. Its pathogenesis is complex, and there is currently no cure. The rapid progress in multi-omics technologies has provided new tools to uncover the intricate pathological mechanisms underlying migraine. This systematic review aims to synthesize the findings of multi-omics studies on migraine to further elucidate the complex mechanisms of disease onset, thereby laying a scientific foundation for identifying new therapeutic targets.METHODS: We conducted a comprehensive systematic review, specifically focusing on clinical observational studies that investigate various aspects of migraine through the integration of genomics, transcriptomics, proteomics, and metabolomics. Our search encompassed multiple databases including PubMed, EMBASE, the Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang database, and the China Biology Medicine Database to cover studies from database inception until 20 March 2024., The scope of our review included various aspects of migraine such as ictal and interictal phases; episodic or chronic migraine; menstrual-related migraine; and migraine with or without aura (PROSPERO registration number: CRD42024470268).RESULTS: A total of 38 studies were ultimately included, highlighting a range of genetic variations, transcriptional abnormalities, protein function alterations, and disruptions in metabolic pathways associated with migraine.These multi-omics findings underscore the pivotal roles played by mitochondrial dysfunction, inflammatory responses, and oxidative stress in the pathophysiology of migraine.CONCLUSION: Multi-omics approaches provide novel perspectives and tools for comprehending the intricate pathophysiology of migraine, facilitating the identification of potential biomarkers and therapeutic targets.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=470268, identifier CRD42024470268.PMID:39850553 | PMC:PMC11754399 | DOI:10.3389/fphar.2024.1452614

Multidrug efflux pumps of <em>Pseudomonas aeruginosa</em> show selectivity for their natural substrates

Fri, 24/01/2025 - 12:00
Front Microbiol. 2025 Jan 9;15:1512472. doi: 10.3389/fmicb.2024.1512472. eCollection 2024.ABSTRACTAntibiotic-resistant Gram-negative bacteria are an increasing threat to human health. Strategies to restore antibiotic efficacy include targeting multidrug efflux pumps by competitive efflux pump inhibitors. These could be derived from natural substrates of these efflux systems. In this work, we aimed to elucidate the natural substrates of the clinically relevant Mex efflux pumps of Pseudomonas aeruginosa by an untargeted metabolomic approach. We constructed a PA14 mutant, genetically deleted in the major multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexXY-OprM, and MexEF-OprN and expressed in this mutant each efflux pump individually from an inducible promoter. Comparative analysis of the exo-metabolomes identified 210 features that were more abundant in the supernatant of efflux pump overexpressors compared to the pump-deficient mutant. Most of the identified features were efflux pump specific, while only a few were shared among several Mex pumps. We identified by-products of secondary metabolites as well as signaling molecules. Supernatants of the pump-deficient mutant also showed decreased accumulation of fatty acids, including long chain homoserine lactone quorum sensing molecules. Our data suggests that Mex efflux pumps of P. aeruginosa appear to have dedicated roles in extruding signaling molecules, metabolic by-products, as well as oxidized fatty acids. These findings represent an interesting starting point for the development of competitive efflux pump inhibitors.PMID:39850140 | PMC:PMC11754269 | DOI:10.3389/fmicb.2024.1512472

Metabolomics-based study on the effect of low-voltage electrostatic field treatment on the storage quality of postharvest square bamboo shoots

Fri, 24/01/2025 - 12:00
Food Chem X. 2024 Dec 31;25:102143. doi: 10.1016/j.fochx.2024.102143. eCollection 2025 Jan.ABSTRACTLow-voltage electrostatic field (LP) enhances the freezing quality of food by increasing water supercooling and improving ice crystal morphology. This study explored the effects of LP treatment on the storage quality of square bamboo shoots using physicochemical, gas chromatography-mass spectrometry, and metabolomics methods. Results showed that with prolonged storage, the LP-treated group had lower activities of peroxidase, phenylalanine ammonia-lyase, and lower levels of malondialdehyde, cellulose, and lignin compared to the control group, while superoxide dismutase and catalase activities and shear force values were higher. LP treatment also increased the levels of hexanol, (E)-2-hexenal, and azelaic acid, promoted the production of 2-nonanol and (Z)-2-heptenal, and inhibited the reduction of DL-malic acid, methionine, and the increase of L-phenylalanine and 4-coumaric acid. These changes were closely related to fatty acid metabolism, TCA cycle, and phenylalanine metabolism pathways. Overall, LP treatment can effectively improve the storage quality of square bamboo shoots.PMID:39850054 | PMC:PMC11754678 | DOI:10.1016/j.fochx.2024.102143

Continuous carbon source supply is essential for high rifamycin productivity of Amycolatopsis mediterranei in nitrate-stimulated fermentation revealed by a metabolomic study

Fri, 24/01/2025 - 12:00
Acta Biochim Biophys Sin (Shanghai). 2025 Jan 24. doi: 10.3724/abbs.2024245. Online ahead of print.ABSTRACTAmycolatopsis mediterranei U32 is an industrial strain capable of producing therapeutically useful rifamycin SV. In early days of fermentation studies, nitrate was found to increase the yield of rifamycin along with globally, affecting both carbon and nitrogen metabolism in favor of antibiotic biosynthesis; thus, the nitrate-stimulating effect (NSE) hypothesis was proposed. Although GlnR is likely the master regulator of the pleotropic effect of NSE, the global metabolism affected by NSE has never been systematically examined. In this study, we use mass spectrometry-based metabolomics to quantitatively monitor the metabolomic responses of A. mediterranei U32 to nitrate supplementation. The concentrations of many metabolites involved in central carbon metabolism, including glucose 6-phosphate, glucose 1-phosphate, UDP-glucose, and acetyl-coenzyme A, decrease significantly after the addition of 80 mM potassium nitrate to the medium. We find that the rifamycin SV production yield could be increased by the addition of glucose during the logarithmic growth phase. Moreover, at multiple time points during glucose supplementation in the mid- and late-exponential phases, the yield of rifamycin SV further increases, reaching 354.3%. Quantitative real-time PCR assays of the key genes corresponding to the synthesis of the rifamycin SV precursor combined with data from metabolomics analysis confirm that carbon source deficiency is compensated for after glucose supplementation and that the expression of genes involved in the pathway of 3-amino-5-hydroxybenzoic acid synthesis by UDP-glucose and glutamine is significantly increased. This preliminary exploration of dynamic metabolomic profiles has the potential to increase our understanding of the NSE.PMID:39849912 | DOI:10.3724/abbs.2024245

Relationship between Abnormal Lipid Metabolism and Gallstone Formation

Fri, 24/01/2025 - 12:00
Korean J Gastroenterol. 2025 Jan 25;85(1):11-21. doi: 10.4166/kjg.2024.135.ABSTRACTCholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.PMID:39849808 | DOI:10.4166/kjg.2024.135

Aroma analysis and biomarker screening of 27 tea cultivars based on four leaf color types

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115681. doi: 10.1016/j.foodres.2025.115681. Epub 2025 Jan 6.ABSTRACTGreen is no longer the only color used to describe tea leaves. As tea plants with different leaf colors-white, yellow, and purple-yield significant economic benefits, scholars are growing increasingly curious about whether these differently colored leaves possess unique aromatic characteristics. Headspace solid-phase microextraction (HS-SPME) combined with GC-MS was used to analyze the volatile metabolites of buds and leaves from 7 white-leaf tea plants, 9 yellow-leaf tea plants, 4 purple-leaf tea plants, and 7 normal (green) tea plants. A total of 125 aroma metabolites were identified. The aroma compounds of heterochromatic tea leaves and green-leaf tea were compared separately. It was found that white-leaf tea had the most upregulated compounds (63 up), mainly floral and fruity aromas, including nerol, Z-isogeraniol, and E-3-hexen-1-yl acetate. Purple-leaf tea had the most downregulated compounds (31 down), including β-myrcene, benzyl alcohol, and methyl salicylate, which are related to fresh and fruity aromas. According to variable importance in projection (VIP > 1) and a p-value < 0.05, a total of 40 differential compounds were detected, among which Z-3-hexenol, 1-nonanol, 2,4-di-tert-butylphenol, and 2,6,10,15-tetramethyl-heptadecane were common in all heterochromatic tea. The random forest model constructed using differential metabolites screened out five aroma metabolites, including Z-3-hexenyl isobutyrate, E-3-hexen-1-yl acetate, 2,4-di-tert-butylphenol, Z-jasmone, and Z-isogeraniol. These metabolites demonstrated high accuracy in the model (AUC = 1) and have the potential to serve as characteristic aroma compounds for distinguishing tea leaf colors.PMID:39849798 | DOI:10.1016/j.foodres.2025.115681

Microbiota dynamics and metabolic mechanisms in fermented sausages inoculated with Lactiplantibacillus plantarum and Staphylococcus xylosus

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115680. doi: 10.1016/j.foodres.2025.115680. Epub 2025 Jan 5.ABSTRACTLactiplantibacillus plantarum and Staphylococcus xylosus are common starters for fermented sausages. Several studies have demonstrated the impact of these two strains on the quality of fermented sausages. However, the mechanism underlying the effects of these two microorganisms on co-cultivation in sausages remains unclear. This study aimed to investigate the effects of inoculation with various combinations of starters on the microbial communities and metabolic profiles of fermented sausages. High-throughput sequencing revealed that, during sausage fermentation, Firmicutes was the dominant bacterial phylum, and the primary microorganisms were Lactococcus, Staphylococcus, Lactobacillus, and Pseudomonas. On the last day of fermentation, the highest abundance of Staphylococcus was observed in the co-inoculation group. Furthermore, inoculated fermentation effectively inhibited the growth of pathogenic and spoilage bacteria. Metabolomic analysis of the four groups of samples identified 208 metabolites in positive ion mode and 109 in negative ion mode. A total of 31 differential metabolites were identified (P < 0.05, variable importance in the projection >1.5), primarily benzene and substituted derivatives, carboxylic acids and derivatives, and fatty acyls. Five crucial differential metabolites (subaphylline, naringenin, 1-hexadecanol, beta-alanyl-L-lysine, and 3'-AMP) were identified as potential biomarkers for fermented sausages. Key differential metabolite metabolic pathways indicated that L. plantarum YR07 dominated in metabolite regulation during sausage fermentation, and S. xylosus Y-18 downregulated the fatty acid degradation pathway, which also affected the metabolism of fermented sausages. Co-cultivation of the two bacteria exhibited a synergistic effect on the metabolism of the fermented sausages. This study offers further insights into improving the quality of fermented sausages, thereby establishing a theoretical foundation for the production of excellent fermenters.PMID:39849797 | DOI:10.1016/j.foodres.2025.115680

Dynamics of microbial communities and metabolites during the fermentation of Ningxia goji berry wine: An integrated metagenomics and metabolomics approach

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115609. doi: 10.1016/j.foodres.2024.115609. Epub 2024 Dec 30.ABSTRACTNingxia Goji Berry Wine (NGBW), a traditional Chinese fermented beverage, exhibits complex flavor quality changes during fermentation, the mechanisms of which remain insufficiently elucidated. This study aimed to elucidate the dynamic shifts in physicochemical properties, metabolites, and microbial communities throughout the controlled fermentation process of NGBW. Metabolomic analysis identified 8 key differential volatile metabolites (VOCs) and 406 differential non-volatile metabolites. The enrichment analysis of KEGG metabolic pathways revealed that, during the fermentation of NGBW, ten critical metabolic pathways-Purine metabolism, Glycine, Serine, and Threonine metabolism, Galactose metabolism, and the Citric Acid (TCA) Cycle-play essential roles. Amplicon sequencing indicated that 25 bacterial genera dominated the microbial ecosystem (relative abundance ≥ 0.1 %). Spearman correlation analysis revealed significant associations between 5 core microorganism and flavor compounds, and 25 core microbes with non-volatile metabolites, suggesting their pivotal roles in flavor formation. This study provides a theoretical basis for optimizing the fermentation process and enhancing the flavor quality of NGBW.PMID:39849759 | DOI:10.1016/j.foodres.2024.115609

Multi-Omics analysis reveals the sensory quality and fungal communities of Tibetan teas produced by wet- and dry-piling fermentation

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115690. doi: 10.1016/j.foodres.2025.115690. Epub 2025 Jan 6.ABSTRACTYa'an Tibetan tea, a dark tea with a rich historical heritage, is typically processed using two primary piling fermentation methods: wet piling with rolled leaves (moisture content around 60%) and dry piling with sun-dried or baked green tea leaves (moisture content below 30%). This study employed sensory evaluation, targeted and non-targeted metabolomics, and fungal Internal Transcribed Spacer (ITS) sequencing to investigate changes in quality components and fungal composition in Tibetan tea processed by both wet and dry-piling methods. The results revealed that 3,7-Dimethyl-1,5,7-octatriene-3-ol and D-limonene were identified as key volatile metabolites contributing to the aroma variations between the dry and wet-piled teas. More pronounced differences were observed in non-volatile components, with 407 differential metabolites identified between the wet- and dry-piled teas. Linear discriminant analysis effect size (LEfSe) identified Rhizomucor, Aspergillus, Thermomyces, Setophoma, and Debaryomyces as the key fungal genera with significant differences between the two piling methods, also dominating in abundance and playing a crucial role in the fermentation process of Tibetan tea. Correlation analysis between microbial communities and differential metabolites showed that Debaryomyces, Thermomyces, and Setophoma were significant contributors to the aroma differences between the teas produced by the two piling methods, while Rhizomucor and Aspergillus had a greater influence on non-volatile metabolites. Since Rhizomucor and Aspergillus were the most dominant fungi in the wet (63.05%) and dry-piled (68.70%) samples, respectively, and showed opposite correlations with major non-volatile differential metabolites, they may underlie the flavor differences between the two piled teas, such as mellowness, thickness, and sweet aftertaste. This study sheds light on the chemical and fungal mechanisms underlying the quality formation of Ya'an Tibetan tea processed by wet and dry piling methods, providing theoretical guidance for the improvement, standardization, and potential enhancement of production efficiency of Ya'an Tibetan tea production.PMID:39849727 | DOI:10.1016/j.foodres.2025.115690

Metabolomics and ionomics reveal the quality differences among peach, acacia and karaya gums

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115559. doi: 10.1016/j.foodres.2024.115559. Epub 2024 Dec 30.ABSTRACTDespite the diverse industrial applications and health benefits of plant gums, significant variations in quality among different types remain underexplored. This study investigates the differences in antioxidant activity, mineral elements, and metabolic profiles among peach, acacia, and karaya gums. Our findings reveal significant differences in total phenol content, with peach gum exhibiting the highest (20.41 μmol/g), followed by acacia gum (3.94 μmol/g) and karaya gum (1.24 μmol/g). Metabolomics and ionomics show that these gums were rich in a variety of small molecular metabolites, including amino acids, organic acids, flavonoids, and lipids, as well as numerous mineral elements. However, the concentrations of these compounds varied significantly across the different gum types. Specifically, peach gum contained higher levels of small-molecule organic acids (such as citric, quinic, and azelaic acids) and flavonoids. In contrast, acacia gum was characterized by a higher content of central amino acids (glutamic and aspartic acids), aromatic amino acids (tyrosine, phenylalanine and tryptophan) and alkaloids (trigonelline, spermidine and spermine). Karaya gum exhibited higher levels of lipids (including palmitic, linoleic, and tetradecanoic acids) and minerals (such as Ca, S, Mg and Fe). Notably, pesticide residues, including thiamethoxam, propiconazole, and difenoconazole, were detected in peach gum, indicating potential health risks. These findings provide valuable insights into the quality analysis of plant gums and the exploration of their functional components.PMID:39849709 | DOI:10.1016/j.foodres.2024.115559

Impact of β-casein variants on the formation of β-casomorphins in blue cheeses: Investigating key drivers through peptidomic analysis

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115556. doi: 10.1016/j.foodres.2024.115556. Epub 2025 Jan 4.ABSTRACTβ-Casomorphins (BCMs), food-associated peptides resulting from the proteolytic cleavage of β-casein (β-CN), have been widely investigated for their opioid-like activity. This research aimed to identify the presence of BCM7, BCM6, and BCM5 in different bovine milk-deriving blue cheese types and to describe the intricate mechanisms behind their formation, focusing on their origin from cheese with β-CN A1 and A2 variants. Using nanoLC-ESI-Q-Orbitrap-MS/MS and advanced computational tools, we explored the peptidomes of Bleu d'Auvergne, Gorgonzola, Stilton, and Bergader blue cheeses from milk containing both β-CN A1 and A2 variants. This integrated approach ascertained the occurrence of BCM7 in all cheese samples, although at different concentrations. Evidence demonstrated that all cheeses containing β-CN A1 and A2 variants exhibited proteolysis, resulting in a pronounced BCM7 release because of the concerted activity of multiple Penicillium roqueforti exopeptidases. This study provides insights into the processes underpinning the formation of BCM7, BCM6 and BCM5 in various blue cheese types, identifying putative molecular determinants that might govern the proteolytic release of BCMs from both β-CN A1 and A2 variants as well as the complex interplay between mold peptidases and cheese polypeptide substrates.PMID:39849707 | DOI:10.1016/j.foodres.2024.115556

The processing of shaking and standing improves the taste quality of summer black tea

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115545. doi: 10.1016/j.foodres.2024.115545. Epub 2024 Dec 30.ABSTRACTShaking and standing (SS) enhances the aroma intensity and quality of black tea (BT). However, its contribution to the taste remains unknown, and the interaction mechanism between the aroma and taste perception of black tea is also undisclosed. Here, the metabolomics and sensory evaluation-assisted flavor analysis were employed to investigate the changes in non-volatiles induced by SS, and the interaction mechanism between aroma and taste perception. SSBT exhibited considerable reduced bitterness and astringency intensities compared to BT. Notably, the concentrations of contributing compounds such as catechins, proanthocyanidins, theaflavins, anthocyanins, and flavonol glycosides were decreased in SSBT. Sensory experiments further revealed that nine floral and sweet odorants in SSBT exhibited odor-enhancing interactions. Molecular docking validated the binding affinity and interaction forces between mono/di-ligands and OR1G1/OR52D1. Furthermore, the presence of the nine odorants exerted inhibitory effects on the bitterness and astringency of SSBT. These findings provide a novel perspective on the formation of flavor in SSBT.PMID:39849699 | DOI:10.1016/j.foodres.2024.115545

Integrated metabolome and transcriptome analysis provides insights into the mechanisms of terpenoid biosynthesis in tea plants (Camellia sinensis)

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115542. doi: 10.1016/j.foodres.2024.115542. Epub 2024 Dec 30.ABSTRACTVolatile terpenoids are major substances responsible for the floral and fruity scents of teas. However, little is known about the regulatory mechanisms of terpenoid biosynthesis pathways in tea plants. 'Zhenfeng Yesheng tea' (ZFYS), a distinctive tea tree germplasm resource in Guizhou province, is known for its unique flavor characterized by a mellow taste and a floral aroma. Here, we conducted metabolome and transcriptome analyses of 'ZFYS', 'Jinguanyin tea' (JGY), and 'Longjing 43 tea' (LJ43) leaves to obtain the global correlation of MYB TFs with terpene synthase (TPS) genes and differential accumulated metabolites. In total, 292 differentially accumulated metabolites (DAMs) were identified and chemically classified, with 26.37% of them being terpenoids. Among these, 33 key volatile terpenoids significantly accumulated in 'ZFYS', 'LJ43', and 'JGY' leaves, mainly contributing to the floral and sweet scents. In addition, a total of 6330, 7238, and 8557 unigenes were obtained in "JGY vs LJ43", "ZFYS vs JGY", and "ZFYS vs LJ43" comparisons, respectively. The results of transcriptome analysis, correlation analysis, and quantitative real-time PCR (qRT-PCR) analysis revealed significant correlations between candidate CsTPSs and CsMYBs. The expression levels of CsMYB59, CsMYB167 and CsMYB178 showed that they had a strong positive correlation with CsTPS01, -03, -15, -53, -69 and -79, suggesting their potential function in regulating sesquiterpenoid biosynthesis. In conclusion, this study provides comprehensive metabolomics and transcriptomics profiles of the germplasm of 'ZFYS' tea plants and reveals the underlying key genes involved in volatile terpenoid biosynthesis.PMID:39849697 | DOI:10.1016/j.foodres.2024.115542

Non-targeted metabonomics reveals the effect of linalyl alcohol on Brochothrix thermophile and its potential application

Fri, 24/01/2025 - 12:00
Food Res Int. 2025 Feb;201:115549. doi: 10.1016/j.foodres.2024.115549. Epub 2024 Dec 30.ABSTRACTBrochothrix thermophcta (B. thermophcta) is a pathogenic microorganism associated with food contamination. Linalyl alcohol, owing to its broad spectrum and exceptional antibacterial properties, is regarded as a potent natural antimicrobial agent. This is to elucidate the cellular-level mechanism of linalyl alcohol on B. thermophacta and investigate, for the first time, its regulatory effect on the metabolic pathway of B. thermophacta through metabonomics analysis. The results demonstrated that treatment with linalyl alcohol led to a reduction in bacterial metabolic capacity, while simultaneously promoting an increase in membrane fluidity through damage to the bacterial cell membrane. A total of 201 differential metabolites were identified at the metabolic level, with 50 showing significant up-regulation and 151 displaying significant down-regulation. The differential metabolites primarily participate in the tRNA cycle, amino acid metabolism, nucleotide metabolism, and aminoacyl-tRNA biosynthesis, with a particular emphasis on the significant impairment of amino acid metabolism. The application results demonstrated that linalyl alcohol exhibited a significant antibacterial effect on B. thermosphacta, as evidenced by the negligible changes observed in the color, smell, and tissue state of pork even after 8 days of treatment. In summary, linalyl alcohol exhibits multi-target and multi-pathway inhibition against B. thermosphacta, leading to disruption of cell morphology and metabolic processes. These findings provide a novel theoretical foundation for understanding the inhibitory mechanism of linalyl alcohol on B. thermosphacta, highlighting its potential as an effective alternative to food additives in the preservation industry of livestock products.PMID:39849689 | DOI:10.1016/j.foodres.2024.115549

Magnesium ions regulate the Warburg effect to promote the differentiation of enteric neural crest cells into neurons

Fri, 24/01/2025 - 12:00
Stem Cell Res Ther. 2025 Jan 23;16(1):19. doi: 10.1186/s13287-024-04121-4.ABSTRACTBACKGROUND: Understanding how enteric neural crest cells (ENCCs) differentiate into neurons is crucial for neurogenesis therapy and gastrointestinal disease research. This study explores how magnesium ions regulate the glycolytic pathway to enhance ENCCs differentiation into neurons.MATERIALS AND METHODS: We used polymerase chain reaction, western blot, immunofluorescence, and multielectrode array techniques to assess magnesium ions' impact on ENCCs differentiation. Non-targeted metabolomic sequencing, cellular acidification rate, oxygen consumption, and western blot analyzed sugar metabolism changes. D-glucose-13C6 isotope tracing identified key glucose flux changes. Surface plasmon resonance was used to detect the binding affinity of magnesium ions with key glycolysis genes. The elastic modulus of the hydrogel was measured using a universal testing machine, while pore size and porosity were assessed with scanning electron microscopy. Swelling ratios were determined using gravimetric analysis. In vivo, ENCCs in hydrogels were transplanted into renal capsule and subcutaneously, and magnesium ions' effects on ENCCs differentiation were evaluated.RESULTS: Magnesium ions increased glycolysis levels during ENCCs differentiation into neurons, along with significant upregulation of neuronal markers β-Tubulin and ubiquitin C-terminal hydrolase L1, and enhanced functional neuronal properties. D-glucose-13C6 tracing results showed increased carbon flux in the glycolytic pathway after magnesium supplementation. The binding affinity of magnesium ions with the glycolytic key enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was found to be 1.08 μM. Inhibiting glycolysis suppressed ENCCs differentiation into neurons, emphasizing its crucial role. The double-cross-linked hydrogel gelatin methacryloyl-alginate (gelMA-ALMA), cross-linked with magnesium ions, showed promise in enhancing ENCCs differentiation in vivo without causing systemic hypermagnesemia.CONCLUSION: Magnesium ions promote ENCCs differentiation into neurons by activating the Warburg effect. The GelMA-ALMA hydrogel serves as an effective localized magnesium delivery system, supporting neuronal differentiation in vivo.PMID:39849616 | DOI:10.1186/s13287-024-04121-4

Antimicrobial activity of adipose-derived mesenchymal stromal cell secretome against methicillin-resistant Staphylococcus aureus

Fri, 24/01/2025 - 12:00
Stem Cell Res Ther. 2025 Jan 23;16(1):21. doi: 10.1186/s13287-025-04138-3.ABSTRACTBACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is still a growing concern in the field of antimicrobial resistance due to its resistance to conventional antibiotics and its association with high mortality rates. Mesenchymal stromal cells (MSCs) have been shown as a promising and attractive alternative treatment for bacterial infections, due to their antibacterial properties and potential to bypass traditional resistance mechanisms. This study aims to shed light on the antibacterial potential of adipose-derived mesenchymal stromal cell (AD-MSC) secretome against clinical isolates of Staphylococcus spp., including MRSA strains.METHODS: Using the Kirby-Bauer disk diffusion method, broth microdilution assays, and colony-forming unit (CFU) counting, the antibacterial activity of AD-MSC secretome was assessed. These tests were first conducted on Staphylococcus (S.) aureus ATCC 25923, then on 73 clinical isolates including MRSA strains. Further molecular analysis was performed to identify resistant genes in MRSA isolates.RESULTS: The AD-MSC secretome demonstrated significant antibacterial activity against S. aureus ATCC with a 32 mm inhibition zone. 96% of the collected staphylococcal clinical isolates showed susceptibility to the secretome with 87.5% inhibition observed in MRSA isolates, along with 100% in MSSA, MSSE, and MRSE strains. Molecular analysis revealed that MRSA strains resistant to the secretome harbored mecA, ermA, and ermB genes. Additionally, the mecA-negative MRSA strains remained susceptible to the secretome, suggesting alternative resistance mechanisms.CONCLUSION: These findings emphasize the ability of AD-MSCs secretome as a promising alternative for treating antibiotic-resistant infections, with potential applications in combating MRSA. However, further research is required to explore its clinical applications as a complementary or standalone therapy for resistant infections.PMID:39849590 | DOI:10.1186/s13287-025-04138-3

Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis

Fri, 24/01/2025 - 12:00
BMC Ophthalmol. 2025 Jan 23;25(1):43. doi: 10.1186/s12886-025-03875-6.ABSTRACTBACKGROUND: Herpes simplex keratitis (HSK) is a recurrent inflammatory disease of cornea primarily initiated by type I herpes simplex virus infection of corneal epithelium. However, early diagnosis of HSK remains challenging due to the lack of specific biomarkers. This study aims to identify biomarkers for HSK through tear metabolomics analysis between HSK and healthy individuals.METHODS: We conducted a cross-sectional study enrolling 33 participants. Tear samples were collected from one eye of 18 HSK patients and 15 healthy volunteers using Schirmer-strips. Tear metabolomic profiling was performed using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Metabolites were quantified and matched against entries in the human metabolome database (HMDB) and small molecule pathway database (SMPDB) to identify metabolites and metabolic pathways, respectively. Metabolic differences between HSK and control group were determined using multivariate statistical analysis.RESULTS: A total of 329 metabolites were identified, of which 18 were significantly altered in HSK patients. Notably, 12 metabolites were significantly increased, and 6 were significantly decreased in HSK patients. The changed metabolites were enriched in these pathways: arginine and proline metabolism, phospholipid biosynthesis, alpha linolenic acid and linoleic acid metabolism, retinol metabolism. To assess the potential utility of tear biomarkers, a predictive model was developed combining 4 metabolites (AUC = 0.998 [95%CI: 0.975, 1]): D-proline, linoelaidic acid, plantagonine, and phosphorylcholine.CONCLUSIONS: Our study establishes that HSK has a distinctive metabolomic profile, with 4 key elements maybe emerging as potential biomarkers for diagnostic purposes. These findings may provide novel insights into early and rapid diagnosis of HSK.PMID:39849402 | DOI:10.1186/s12886-025-03875-6

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